Evaluating the Antitumor Characteristics and Mechanisms of Prostate-Derived Ets Factor in the Human Prostate

The prostate derived Ets factor (PDEF) is one of the Ets family genes which are regarded as transcription factors regulating a number of biological processes including cell proliferation, differentiation, and invasion. PDEF is an important modulator in the neoplasia process; however, the results of studies concerning the PDEF as the antitumor gene are still contrariety. Moreover, the functions of PDEF in the human prostate are still not well-known. Our previous studies indicated that cardiac glycosides block prostate specific antigen (PSA) expression via downregulation of PDEF gene expression. Forced-overexpression of PDEF increases gene expression of B-cell translocation gene 2 (BTG2), N-myc downstream regulated gene 1 (NDRG1), and Maspin, which attenuated cell proliferation, invasion, and tumorigenesis in prostate carcinoma cells. Results of our preliminary studies also indicated that expression of PDEF may correlate with the epithelial to mesenchymal transition (EMT). Bioflavonoids, such as resveratrol, and retinol acid (vitamin A) may inhibit cell proliferation via inducing PDEF gene expression. The objectives of this three-year proposal are to (1) identify the PDEF as an antitumor gene in the human prostate carcinoma cells and determine the correlation of PDEF expression and pathologic stage of prostate cancer, (2) determine the correlation between EMT and PDEF, (3) identify the target genes of PDEF, and (4) understand the regulatory mechanisms of the PDEF gene in prostate carcinoma cells. PI will use the specimens from patients with prostatic disease, in vivo xenograft animal model, and in vitro cell models to study the functions of PDEF in the prostate. The microarry assays screen will allow PI to discover the unknown and novel PDEF-downstream genes with specific functions. PI will evaluate the effect of p53, bioflavonoids, retinol acid, steroid, and anticancer drugs on PDEF gene expression; moreover, the correlation between PDEF and EMT will also be investigated by immunoblotting, RT-qPCR, and transient gene expression assays. The long-term objects of this proposal are to understand function and the regulatory mechanisms of PDEF gene in the neoplasia of the prostate.

Project ID:PC10401-0163
External Project ID:NSC102-2320-B182-003-MY3